Effect of pH and water-soluble polymers on the aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin derivatives.
The aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin (beta-CD) and its alkyl derivatives hydroxypropyl-beta-CD and methyl-beta-CD was studied. We also investigated the effect of water-soluble polymers, hydroxypropylmethyl-cellulose, sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25 degrees C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. beta-CDs increased the aqueous solubility of nimesulide in the following order: methyl-beta-CD > beta-CD > hydroxypropyl-beta-CD. Addition of hydroxypropylmethyl-cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three beta-CDs with nimesulide, while preheating of the polymer at 70 degrees C under sonication resulted in an additional two-fold increase in the aqueous solubility of the drug. Sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus beta-CD, hydroxypropyl-beta-CD and methyl-beta-CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl-cellulose in order to enhance its oral bioavailability.
Alexanian
Christina
C
Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens 157 71, Greece.
Papademou
Helen
H
Vertzoni
Maria
M
Archontaki
Helen
H
Valsami
Georgia
G
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005079:Excipients / Q000737:chemistry*; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013010:Sonication; D013449:Sulfonamides / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D005079:Excipients; D011108:Polymers; D013449:Sulfonamides; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C031215:betadex; C012655:nimesulide